Body temperature is highly regulated in mammals. However, thermal biology in smaller mammals (such as mice) is different from that in larger mammals (such as adult humans). For example, when mice are singly housed at room temperature, about half of caloric intake is burned to maintain body temperature (facultative thermogenesis), while humans require little facultative thermogenesis. Upon fasting, mice can reduce their body temperature by >10 C, while humans with extreme starvation lower body temperature by only 0.2 C. We are exploring the use of body temperature as an indicator of the perceived metabolic status of the mouse. For example, what is the effect on body temperature of a genetic manipulation or drug treatment? What genetic manipulations or drug treatments cause dissociation of body temperature from nutritional status? What are the neurotransmitters and neural mechanisms involved? Progress in FY2014 includes the following: We published a study that MTII, a widely used melanocortin agonist that increases metabolic rate, can also cause a transient hypometabolism and hypothermia. We propose that the hypometabolism/hypothermia is a regulated response, potentially beneficial during extreme physiologic stress. We published that the reduced body temperature of Brs3 null mice is more readily detected if body temperature is analyzed as a function of physical activity level and light/dark phase. Physical activity level correlated best with body temperature 4 minutes later. The reduced body temperature in Brs3 null mice is due to altered regulation of energy homeostasis affecting higher center regulation of body temperature, rather than an intrinsic defect in brown adipose tissue. We published a re-examination of chemical uncoupler 2,4-dinitrophenol (DNP) as a treatment for obesity in mice. DNP treatment at thermoneutrality (30 C) increased energy expenditure but did not change food intake and the mice weighed 26% less due to decreased fat mass, without a change in lean mass. DNP improved glucose tolerance and reduced hepatic steatosis without observed toxicity. Body temperature increased slightly (0.22 C) with DNP treatment at thermoneutrality.